[show abstract][hide abstract] ABSTRACT: Lumenal glucose initiates changes in gastrointestinal (GI) function, including inhibition of gastric emptying, stimulation of pancreatic exocrine and endocrine secretion, and intestinal fluid secretion. Glucose stimulates the release of GI hormones and 5-hydroxytryptamine (5-HT), and activates intrinsic and extrinsic neuronal pathways to initiate changes in GI function. The precise mechanisms involved in luminal glucose-sensing are not clear; studying gut endocrine cells is difficult due to their sparse and irregular localization within the epithelium.
Here we show a technique to determine activation of gut epithelial cells and the gut-brain pathway in vivo in rats using immunohistochemical detection of the activated, phosphorylated, form of calcium-calmodulin kinase II (pCaMKII). Key
Perfusion of the gut with glucose (60 mg) increased pCaMKII immunoreactivity in 5-HT-expressing enterochromaffin (EC) cells, cytokeratin-18 immunopositive brush cells, but not in enterocytes or cholecystokinin-expressing cells. Lumenal glucose increased pCaMKII in neurons in the myenteric plexus and nodose ganglion, nucleus of the solitary tract, dorsal motor nucleus of the vagus and the arcuate nucleus. pCaMKII expression in neurons, but not in EC cells, was significantly attenuated by pretreatment with the 5-HT(3) R antagonist ondansetron. Deoxynojirimycin, a selective agonist for the putative glucose sensor, sodium-glucose cotransporter-3 (SGLT-3), mimicked the effects of glucose with increased pCaMKII in ECs and neurons; galactose had no effect.
The data suggest that native EC cells in situ respond to glucose, possibly via SGLT-3, to activate intrinsic and extrinsic neurons and thereby regulate GI function.
Neurogastroenterology and Motility 02/2011; 23(7):e282-93. · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: Although it is well established that the presence of nutrients in the gut lumen can bring about changes in GI function, the mechanisms and pathways by which these changes occur has not been fully elucidated. It has been known for many years that luminal nutrients stimulate the release of hormones and regulatory peptides from gut endocrine cells and that luminal nutrients activate intrinsic and extrinsic neural pathways innervating the gut. Activation of gut endocrine cells and neural pathways by nutrients in the gut lumen is key in coordination of postprandial GI function and also in the regulation of food intake. Recent evidence suggests that these pathways can be modified by long term changes in diet or by inflammatory processes in the gut wall. Thus it is important to determine the cellular and molecular mechanisms underlying these processes not only to increase our understanding of as part of basic physiology but also to understand changes in these pathways that occur in the presence of pathophysiology and disease. This review summarizes some of the latest data that we have obtained, together with information from the other laboratories, which have elucidated some of the mechanisms involved in nutrient detection in the gut wall. The focus is on monosaccharides and protein hydrolysates as there is some evidence for a role for nutrient transporters in detection of these nutrients.
Journal of physiology and biochemistry 01/2009; 64(4):349-56. · 1.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: We have investigated the influence of intravenous corticotropin-releasing factor (CRF) on intraluminal pressure of the body of the stomach and the neurohumoral pathways through which CRF inhibits gastric motor function in rats. CRF (0.21–210 pmol) injected intravenously produced a dose-dependent, long-lasting decrease in baseline tone and inhibited phasic gastric contractions measured manometrically in urethane-anesthetized rats. The inhibitory effect of CRF was abolished by administration of hexamethonium or by subdiaphragmatic vagotomy but was unaffected by perineural treatment of the vagus nerves with capsaicin, adrenalectomy, or celiac/superior mesenteric ganglionectomy. Intravenous administration of CRF (126 pmol) inhibited by 69% the emptying of a noncaloric liquid meal as measured by the phenol red technique in conscious rats. Hexamethonium pretreatment significantly attenuated the CRF -induced delay in gastric emptying; bretylium, naloxone, adrenalectomy, and celiac I superior mesenteric ganglionectomy had no such effect. In an isolated tissue preparation, CRF (10−11 to 10−6 M) inhibited spontaneous, but not carbachol-induced, contractions of rat antral longitudinal muscle. The effect of CRF was dose-dependent and abolished in the presence of tetrodotoxin. These results suggest that peripheral CRF-induced inhibition of corpus and antral motor contractility may mediate delayed gastric emptying via an action involving a nicotinic synapse, presumably in the enteric nervous system, that requires a vagal input. The in vitro studies support the concept that the action of CRF is not direct on smooth muscle but involves neural transmission within the enteric nervous system.
[show abstract][hide abstract] ABSTRACT: Peptide YY (PYY)(3-36), released by intestinal lipid elicits functional effects that comprise the intestinal feedback response to luminal nutrients, but the pathway of action is not fully characterized. The aim of the present study was to determine the role of the apolipoprotein (apo) A-IV-cholecystokinin (CCK)(1) receptor (CCK(1)R) pathway in exogenous PYY(3-36)-induced activation of the gut-brain axis and inhibition of gastric emptying and food intake. PYY(3-36) (5 microg/100 g ip) significantly inhibited gastric emptying of a chow meal in wild-type but not A-IV(-/-) mice andCCK(1)R receptor blockade with devazepide (10 microg/100 g), abolished PYY(3-36)-induced inhibition of gastric emptying. PYY(3-36)-induced inhibition of food intake in both ad libitum-fed and 16-h fasted mice was unaltered in A-IV(-/-) mice, compared with wild-type controls, or by CCK(1)R receptor blockade with devazepide. PYY(3-36) activated neurons in the midregion of the nucleus of the solitary tract (bregma -7.32 to -7.76 mm) in A-IV(+/+) mice; this was measured by immunohistochemical localization of Fos protein. PYY(3-36)-induced Fos expression was significantly reduced by 65% in A-IV(+/+) mice pretreated systemically with the sensory neurotoxin capsaicin (5 mg/100 g), 78% by the CCK(1)R antagonist, devazepide (10 microg/100 g), and 39% by the Y2R antagonist, BIIE0246 (200 and 600 microg/100 g) and decreased by 67% in apo A-IV(-/-) mice, compared with A-IV(+/+) controls. The data suggest a role for apo A-IV and the CCK(1)R in PYY(3-36)-induced activation of the vagal afferent pathway and inhibition of gastric emptying, but this is likely not the pathway mediating the effects of PYY(3-36) on food intake.
[show abstract][hide abstract] ABSTRACT: The presence of glucose in the intestinal lumen elicits a number of changes in gastrointestinal function, including inhibition of gastric emptying and food intake and stimulation of pancreatic and intestinal secretion. The present study tested the hypothesis that Na(+)-glucose cotransporter (SGLT)-3, a member of the SGLT family of transport proteins, is involved in detection of luminal glucose in the intestine. Gastric emptying, measured in awake rats, was significantly inhibited by perfusion of the intestine with glucose (60 and 90 mg); this effect was mimicked by alpha-methyl glucose (nonmetabolizable substrate of SGLT-1 and -3) but not 2-deoxy-d-glucose (substrate for GLUT-2) or isoosmotic mannitol. Gastric motility and intestinal fluid secretion, measured in anesthetised rats, were significantly inhibited and stimulated, respectively, by duodenal glucose but not galactose, which has a much lower affinity for SGLT-3 than glucose. Duodenal glucose but not galactose stimulated the release of 5-HT into mesenteric lymph and stimulated the discharge of duodenal vagal afferent fibers. mRNA for SGLT-3 was identified in the duodenal mucosa. Together these data suggest that detection of glucose in the intestine may involve SGLT-3, possibly expressed by enterochromaffin cells in the intestinal mucosa, and release of 5-HT.
[show abstract][hide abstract] ABSTRACT: Cholecystokinin (CCK), acting at CCK1 receptors (CCK1Rs) on intestinal vagal afferent terminals, has been implicated in the control of gastrointestinal function and food intake. Using CCK1R(-/-) mice, we tested the hypothesis that lipid-induced activation of the vagal afferent pathway and intestinal feedback of gastric function is CCK1R dependent. In anesthetized CCK1R(+/+) ("wild type") mice, meal-stimulated gastric acid secretion was inhibited by intestinal lipid infusion; this was abolished in CCK1R(-/-) mice. Gastric emptying of whole egg, measured by nuclear scintigraphy in awake mice, was significantly faster in CCK1R(-/-) than CCK1R(+/+) mice. Gastric emptying of chow was significantly slowed in response to administration of CCK-8 (22 pmol) in CCK1R(+/+) but not CCK1R(-/-) mice. Activation of the vagal afferent pathway was measured by immunohistochemical localization of Fos protein in the nucleus of the solitary tract (NTS; a region where vagal afferents terminate). CCK-8 (22 pmol ip) increased neuronal Fos expression in the NTS of fasted CCK1R(+/+) mice; CCK-induced Fos expression was reduced by 97% in CCK1R(-/-) compared with CCK1R(+/+) mice. Intralipid (0.2 ml of 20% Intralipid and 0.04 g lipid), but not saline, gavage increased Fos expression in the NTS of fasted CCK1R(+/+) mice; lipid-induced Fos expression was decreased by 47% in CCK1R(-/-) compared with CCK1R(+/+)mice. We conclude that intestinal lipid activates the vagal afferent pathway, decreases gastric acid secretion, and delays gastric emptying via a CCK1R-dependent mechanism. Thus, despite a relatively normal phenotype, intestinal feedback in response to lipid is severely impaired in these mice.
[show abstract][hide abstract] ABSTRACT: Long chain triglyceride (>C12) in the intestinal lumen potently inhibits gastric emptying and acid secretion via the vagal afferent pathway. While the mechanism of inhibition involves the formation of chylomicrons, the essential role of the apolipoprotein apo A-IV is unclear. Using apo A-IV(-/-) mice, we tested the hypothesis that inhibition of gastric emptying and gastric acid secretion in response to dietary lipid is dependent upon apo A-IV. As measured by nuclear scintigraphy in awake mice, gastric emptying of an ingested whole-egg meal was significantly faster in apo A-IV(-/-) knockout versus A-IV(+/+) controls (34 +/- 1 versus 54 +/- 3 min, P < 0.0001). In anaesthetized A-IV(+/+) mice, meal-stimulated gastric acid secretion was 59% inhibited by intestinal lipid infusion; this was abolished in apo A-IV(-/-) mice. Oral gavage of lipid in awake mice activated neurones throughout the nucleus of the solitary tract (NTS) in A-IV(+/+) mice, measured by immunohistochemical localization of Fos protein expression. However, in the mid region of the NTS (bregma -7.32 to -7.76 mm), Fos expression in response to intestinal lipid was significantly decreased by 50% in apo A-IV(-/-) mice compared to A-IV(+/+) controls. We conclude that activation of the vagal afferent pathway and inhibition of gastric function in response to dietary lipid is partly dependent upon apo A-IV.
The Journal of Physiology 12/2005; 569(Pt 3):949-58. · 4.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: Intestinal infusion of protein digests activates a vago-vagal reflex inhibition of gastric motility. Protein digests release cholecystokinin (CCK) from enteroendocrine cells; however, the precise cellular mechanisms leading to vagal afferent activation is unclear. The hypothesis that the oligopeptide transporter PepT1 plays a major role in the initiation of this vago-vagal reflex was tested by recording activation of duodenal vagal afferent activity and inhibition of gastric motility in response to protein hydrolysates in the presence of 4-aminomethylbenzoic acid (4-AMBA), a competitive inhibitor of PepT1, or 4-aminophenylacetic acid (4-APAA), an inactive 4-AMBA analog. Duodenal infusion of the protein hydrolysate increased vagal afferent discharge and inhibited gastric motility; these responses were abolished by concomitant infusion of 4-AMBA, but not 4-APAA. Duodenal infusion with Cefaclor, a substrate of PepT1, increased duodenal vagal afferent activity; Cefaclor and protein hydrolysates selectively activated CCK-responsive vagal afferents. This study demonstrates that products of protein digestion increase spontaneous activity of CCK-sensitive duodenal vagal afferents via a mechanism involving the oligopeptide transporter PepT1.
Journal of Nutrition 07/2005; 135(6):1491-5. · 4.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: Apolipoprotein A-IV (apo A-IV), a peptide expressed by enterocytes in the mammalian small intestine and released in response to long-chain triglyceride absorption, may be involved in the regulation of gastric acid secretion and gastric motility. The specific aim of the present study was to determine the pathway involved in mediating inhibition of gastric motility produced by apo A-IV. Gastric motility was measured manometrically in response to injections of either recombinant purified apo A-IV (200 microg) or apo A-I, the structurally similar intestinal apolipoprotein not regulated by triglyceride absorption, close to the upper gastrointestinal tract in urethane-anesthetized rats. Injection of apo A-IV significantly inhibited gastric motility compared with apo A-I or vehicle injections. The response to exogenous apo A-IV injections was significantly reduced by 77 and 55%, respectively, in rats treated with the CCK(1) receptor blocker devazepide or after functional vagal deafferentation by perineural capsaicin treatment. In electrophysiological experiments, isolated proximal duodenal vagal afferent fibers were recorded in vitro in response to close-arterial injection of vehicle, apo A-IV (200 microg), or CCK (10 pmol). Apo A-IV stimulated the discharge of duodenal vagal afferent fibers, significantly increasing the discharge in 4/7 CCK-responsive units, and the response was abolished by CCK(1) receptor blockade with devazepide. These data suggest that apo A-IV released from the intestinal mucosa during lipid absorption stimulates the release of endogenous CCK that activates CCK(1) receptors on vagal afferent nerve terminals initiating feedback inhibition of gastric motility.
[show abstract][hide abstract] ABSTRACT: The ability to make repetitive non-invasive measurements of gastric emptying of nutritive solids in awake, unstressed mice is highly desirable. The aim of the present study was to develop such a technique using nuclear scintigraphy and diets differing in triglyceride content. Awake mice were accustomed to light restraint and to feeding cooked, egg white (0.00 g fat g(-1)), whole egg (0.10 g fat g(-1)), or egg yolk (0.31 g fat g(-1)). Gastric emptying of each diet was measured by labelling the test meals with Technetium(99m) Mebrofenin and using a conventional gamma camera equipped with a high resolution, parallel hole collimator. Gastric emptying of cooked whole egg was also determined following administration of either vehicle or CCK A receptor antagonist, devazepide. The half-emptying time (t(1/2)) significantly increased with increasing triglyceride content from 14 +/- 5 min to 51 +/- 6 min and 82 +/- 4 min for egg white, whole egg and egg yolk, respectively. Administration of devazepide significantly decreased t(1/2) of whole egg to 28 +/- 2 min. These results demonstrate the sensitivity and predictability of this technique in mice and importantly, provide an opportunity to alter the macronutrient or caloric content of the meal to determine effects on gastric emptying.
Neurogastroenterology and Motility 09/2004; 16(4):421-7. · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: Galanin actions are mediated by distinct galanin receptors (GAL-R), GAL-R1, -R2 and -R3. We investigated the role of GAL-R1 in gastric motility and the expression of GAL-R1 in the rat stomach. In vivo, in urethane-anaesthetized rats, galanin (equipotent for all GAL-Rs) induced a short inhibition of gastric motility, followed by increase in tonic and phasic gastric motility; the latter was significantly reduced by the GAL-R1 antagonist, RWJ-57408. Galanin 1-16 (high affinity for GAL-R1 and -R2) induced a long-lasting decrease of intragastric pressure, which was not modified by RWJ-57408. In vitro, galanin and galanin 1-16 induced increase of intragastric pressure that was not affected by RWJ-57408. Tetrodotoxin (TTX) did not suppress the galanin excitatory effect, whereas the effect of galanin 1-16 on gastric contraction was increased by TTX- or N-nitro-L-arginine, an inhibitor of nitric oxide synthase. GAL-R1 immunoreactivity was localized to cholinergic and tachykinergic neurons and to neurons immunoreactive for nitric oxide synthase or vasoactive intestinal polypeptide. This study suggests that an extrinsic GAL-R1 pathway mediates the galanin excitatory action, whereas an extrinsic, non GAL-R1 pathway is likely to mediate the galanin inhibitory effect in vivo. GAL-R1 intrinsic neurons do not appear to play a major role in the control of gastric motility.
Neurogastroenterology and Motility 09/2004; 16(4):429-38. · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: The enteric nervous system in combination with inputs from parasympathetic and sympathetic nerves regulate the contractile, secretory and vasomotor activity of the gastrointestinal track via neural reflexes. Sensory elements which may be present in specialized neurones, enteroendocrine cells or mast cells detect changes in force, chemical composition or even foreign antigens. Sensory elements signal the enteric nervous system to correct these changes by altering contractile activity, secretion and blood flow. Advances have been made in understanding the sensory mechanisms that are involved in 5-hydroxytryptamine (5-HT) release from enterochromaffin cells (EC) or a model for EC cells. These advances relate to roles for ATP and its metabolites ADP and adenosine in mechanotransduction and a role for a sodium glucose cotransporter, a SGLT-like protein, in chemotransduction.
[show abstract][hide abstract] ABSTRACT: Immunohistochemistry and confocal microscopy were used to investigate mu opioid receptor (muOR) internalization in enteric neurons of the guinea-pig ileum following abdominal surgery. The following surgical procedures were performed under halothane or isofluorane anesthesia: a) midline abdominal skin incision, b) laparotomy or c) laparotomy with intestinal manipulation. Gastrointestinal transit was evaluated by using a non-absorbable marker and measuring fecal pellet output. In neurons from normal and control (anesthesia alone) animals, muOR was predominantly at the cell surface. muOR endocytosis following skin incision was not significantly different from controls (21.2+/-3.5% vs. 13.7+/-2.1%, mean+/-S.E.M.), whereas it was significantly increased by laparotomy (46.5+/-6.1%; P<0.01 vs. controls) or laparotomy plus intestinal manipulation (40.5+/-6.1%; P<0.01 vs. controls) 30 min following surgery compared with controls. muOR endocytosis remained elevated at 4 h (38.6+/-1.2%; P<0.01 vs. controls), whereas it was similar to controls at 6 and 12 h (17.5+/-5.8% and 11.2+/-3.0%). muOR endocytosis occurred in cholinergic and nitrergic neurons. Gastrointestinal transit was significantly delayed by laparotomy or laparotomy plus intestinal manipulation (12.8+/-1.2 and 13.8+/-0.6 h vs. 7.0+/-0.5 in controls; P<0.01), but was not significantly changed by skin incision (8.2+/-0.6 h). The findings of the present study support the concept that the noxious stimulation caused by abdominal surgery induces release of endogenous opioids thus resulting in muOR endocytosis in neurochemically distinct enteric neurons. muOR internalization can serve as indirect evidence of opioid release and as a means to visualize neuronal pathways activated by opioids.
[show abstract][hide abstract] ABSTRACT: Abstract In a number of different experimental paradigms of somatic pain, there is evidence for a vagally mediated antinociceptive system. This pathway probably involves opioid mechanisms. However, whether this pathway is activated in visceral pain or if it involves subdiaphragmatic vagal afferents is unclear. The aim of the present study was to determine whether subdiaphragmatic vagal afferents mediate antinociception in response to a visceral stimulus and whether this involves an opioid pathway. Colorectal distension was performed in fasted, conscious male Sprague-Dawley rats using a balloon catheter connected to an electronic distension device. The number of abdominal contractions (visceromotor response) in response to a tonic colorectal distension (60 mmHg for 10 min) was recorded. Experiments were performed in sham or subdiaphragmatically vagotomized, perineural vehicle- or capsaicin-treated rats (to functionally denervate vagal afferents) before and after administration of naloxone (25 mg kg(-1) bodyweight intraperitoneally). Vagotomy, capsaicin and naloxone pretreatments all significantly enhanced the visceromotor response to colorectal distension. The effect of naloxone in capsaicin-treated rats did not appear to be additive. These results suggest that activation of subdiaphragmatic afferents, which can be blocked by capsaicin, may play a role in opioid-dependent antinociceptive pathways activated by a noxious visceral stimulus.
Neurogastroenterology and Motility 09/2002; 14(4):403-8. · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: The possible mechanisms that may be involved in nutrient detection in the wall of the gastrointestinal tract are reviewed. There is strong functional and electrophysiological evidence that both intrinsic and extrinsic primary afferent neurones mediate mechano- and chemosensitive responses in the gastrointestinal tract. This review focuses on the extrinsic afferent pathways as these are the ones that convey information to the central nervous system which is clearly necessary for perception to occur.
Gut 08/2002; 51 Suppl 1:i11-4. · 10.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: CCK-A receptors and neurons of the nucleus of the solitary tract (NTS) are involved in the regulation of food intake, and in rats, there is evidence for involvement of an intestinal vagal afferent pathway. Studies investigating the role of CCK-A receptors in activation of NTS neurons using highly selective CCK-A receptor agonists and antagonists have yielded conflicting data. In the present study, we investigated CCK-induced and postprandial activation of NTS neurons, together with food intake studies, in CCK-A receptor-deficient Otsuka Long-Evans Tokushima fatty (OLETF) rats. Activated NTS neurons were detected using immunohistological staining for c-Fos protein. Exogenous CCK increased the number of c-Fos protein-positive cells in the NTS of Sprague-Dawley and CCK-A receptor-intact Long-Evans Tokushima Otsuka (LETO) rats but had no effect in CCK-A receptor-deficient OLETF rats. Food intake-induced c-Fos protein expression in NTS neurons was significantly reduced in CCK-A receptor-deficient OLETF rats compared with Sprague-Dawley or LETO rats. Postprandial c-Fos protein expression in the NTS was also significantly decreased after pretreatment with the CCK-A receptor antagonist MK329 after both short- and long-term fasting periods. Exogenous CCK decreased cumulative food intake in Sprague-Dawley and LETO rats but not in OLETF rats. These data demonstrate that CCK-A receptors are involved in the CCK- and food-induced c-Fos protein expression in the NTS. Taken together with the results of the food intake studies, this suggests that activation of CCK-A receptors is involved in the postprandial activation of NTS neurons and in the regulation of food intake.
[show abstract][hide abstract] ABSTRACT: Conflicting reports exist regarding the permanence of improved gastric emptying (GE) after fundoplication for gastroesophageal reflux in children.
Changes in gastric volume (GV) and GE of a radiolabeled mixed meal induced by a Nissen fundoplication (NF) were compared with those with a NF plus pyloroplasty (NF + P). GE was measured preoperatively, 15 and 30 days postoperation, in 24 Sprague-Dawley rats; 12 had NF alone, and 12 had NF + P Results were expressed as percent gastric retention at 90 minutes (GR90). GV was measured at the same time periods in 20 additional rats.
NF rats had enhanced GE with reduction of preoperative GR90 from 37.6% to 23.7% at 15 days (P < .05); however, at 30 days the GR90 increased to 34.3%. NF + P rats had enhanced GE with reduction in GR90 from 37.2% to 20.8% at 15 days (P< .05), which persisted at 30 days (20.4%). Mean GV decreased from (1.36 mL/100 g body weight) preoperation to 0.86 at 15 days (P< .05) at 15 days in the NF group, and returned to 1.29 at 30 days. Mean GV decreased from 1.36 to 0.91 at 15 days in the NF + P rats and persisted at 0.90 at 30 days.
In the rat model, NF enhances GE transiently, whereas NF + P produces long-term enhancement of GE.
Journal of Pediatric Surgery 08/2000; 35(7):1087-90. · 1.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: Two distinct receptors, cholecystokinin (CCK)-A and CCK-B, mediate CCK effects in the digestive system. The aim of this study was to elucidate the cellular sites of expression of CCK-A receptor in the rat stomach and small intestine.
We developed and characterized an antibody to the N-terminal region (LDQPQPSKEWQSA) of rat CCK-A receptor and used it for localization studies with immunohistochemistry.
Specificity of the antiserum was demonstrated by (1) detection of a broad band at 85-95 kilodaltons in Western blots of membranes from CCK-A receptor CHO-transfected cells; (2) cell surface staining of CCK-A receptor-transfected cells, (3) translocation of CCK-A receptor immunostaining in CCK-A receptor-transfected cells after exposure to CCK; and (4) abolition of tissue immunostaining by preadsorbtion of the antibody with the peptide used for immunization. CCK-A receptor immunoreactivity was localized to myenteric neurons and to fibers in the muscle and mucosa. In the stomach, myenteric neurons and mucosal fibers were abundant. Many CCK-A receptor myenteric neurons contained the inhibitory transmitter vasoactive intestinal polypeptide, and some were immunoreactive for the excitatory transmitter substance P. Subdiaphragmatic vagotomy reduced the density of CCK-A receptor fibers in the gastric mucosa by approximately 50%, whereas celiac/superior mesenteric ganglionectomy had no detectable effect on fiber density.
CCK-A receptor is expressed in functionally distinct neurons of the gastrointestinal tract. CCK-A receptor may mediate reflexes stimulated by CCK through the release of other transmitters from neurons bearing the receptor.